The present invention is related to the field of separations in fluidized beds and to beads of a polymer, especially a polysaccharide, into which glass or silica particles, especially quartz particles have been incorporated, and the use of these beads as carrier matrices in stabilized fluidized bed systems, which are characterized by having a low extent of axial dispersion.
It is known that solid entities may be kept suspended above a solid support by bringing the solid entities into a fluid medium (gas or liquid) which is flowing in opposite indirection relative to the gravitational field. A number of particles placed in such a stream of flowing medium in a confined space, such as a cylindrical vessel (column), is commonly referred to as a fluidized bed provided that the particles stay resident in the confined space. This is achieved by balancing the gravitational force versus the frictional, lifting force, exerted by the fluid stream on the solid particles.
Fluidized beds have been used as an efficient means of bringing solid particles in contact with a fluid phase. The relatively high fluid velocities, relative to the particles, allow for efficient mass and heat transfer. Consequently, fluidized beds have been used for combustion and for adsorption processes. Fluidized beds have also been used for culturing of microbial plant or animal cells in so called air-lift reactors. In this case nutritients and dissolved oxygen are brought to the cells and waste products are removed from the cells efficiently because of the efficient mass transfer.
Minor irregularities in the flow field in a fluidized bed cause translational movements of the particles. Over a certain time, there is the same probability that a certain particle may be found at any position within the confined space of the fluidized bed. Here, this effect is referred to as back-mixing or a large degree of axial dispersion. The back-mixing is advantageous when it is desirable to achieve a homogeneous composition of the fluid and solid phases in the entire fluidized bed. However, for adsorption processes, a homogeneous composition is not necessarily advantageous.
In fact, it is possible to obtain a lower concentration of a solute in the effluent fluid if there is no back-mixing than there is with back-mixing in the confined space of the fluidized bed.
In order to prevent complete back-mixing, it has been shown (Buijs (1980)) that screens inserted into the fluidized bed result in a compartmentalization of the bed.
The density, viscosity and the velocity of the fluidium and the diameter and density of the solid entities affect the balancing of frictional versus gravitational forces (Lydersen (1979)). Much lower fluid velocities must be used with liquids than with gases because of the higher densities and viscosities of liquids. In order to reduce mass transfer resistances and to increase through-put (the liquid feed-rate) one may wish to use higher flow rates than those which may be balanced by the gravitational field only. This is possible by applying a third force onto the solid entities. The latter force may be induced by a magnetic field applied to a bed containing ferro- or paramagnetic particles. Such magnetically stabilized fluidized beds have been described (see for instance Burns (1985:1 and 1985:2)). The heat generated by such a system for stabilizing the bed is a clear disadvantage and makes the method less useful especially in temperature sensitive biomolecular systems, even if various cooling systems are available. The need for equipments for generating a magnetic field and for cooling the system increases the process costs considerably.
Particles with relatively lower density and diameter move upwards in the fluidized bed. Consequently, it is possible to feed an unclarified liquid into a fluidized bed containing large diameter and/or high density adsorbent particles without accumulation of solids from the feed in the fluidized bed. The relatively smaller and/or less dense particles originating from the feed stream will be washed out with the effluent provided that the liquid flow-rate is chosen properly. Thus it is possible to improve an adsorptive recovery process starting with an unclarified feed by using a fluidized bed since time, costs and yield reduction caused by a clarification step are avoided. However, since a fluidized bed is back-mixed (unless it is stabilized in some way) the bed is a less efficient adsorber than a packed bed due to the larger axial dispersion in the former. A second reason why the packed bed is more efficient as an adsorber is that the packed bed acts as a multi-step adsorber.
A single step adsorber, such as a fluidized bed, may, on theoretical grounds, be expected to work efficiently if the adsorbing sites have a high binding affinity for a solute, relative to the concentration of the solute in the feed stream. The systems described so far for carrying out separations in a fluidized bed, however, do not fulfil all the demands raised by the users. One problem so far has been that since the beds are not stabilized, flow channels through the bed are easily created, in which the sample molecule might pass with only little chance to be bound.
The beads should be relatively small to allow short diffusion distances, have high density, controlled high sedimentation velocity, being an easily derivatized hydrophilic polymer suitable for applications involving biomolecules.
We have now unexpectedly found that beds may be designed, which combine the advantageous properties of packed beds and fluidized beds. In one aspect of the invention beds are provided which allow relatively less dense and/or relatively smaller particles to pass through the bed with the upward flowing liquid stream since the particles are not packed close together.
By using bead particles covering a given size and/or density interval the particles are kept from moving around in the confined space of the bed such that, for a certain particle the probability to find it in a certain position is high only in a limited volume being a minute fraction of the total bed volume. By keeping the particles resident locally, back-mixing is prevented, thereby reducing axial dispersion and allowing for multistep adsorption without insertion of screens or similar devices.
Furthermore, the beads of the invention are kept suspended in upward flowing liquids without the need for application of heat generating magnetic fields or use of ferro- or paramagnetic additives to the adsorbent particles. In the following the beds achieved when using the actual particles are referred to as stabilized or unmixed expanded beds, which are characterized by having negligible axial dispersion. The axial dispersion is often expressed by the vessel dispersion number (for a definition see Levenspiel (1972)) which in a stabilized bed should be less than about 75xc3x9710xe2x88x923, and especially less than 20xc3x9710xe2x88x923.
The beads according to the invention comprises a polymer matrix into which glass or silica particles, preferably quartz particles are incorporated. The beads may be porous as well as non-porous. The diameter is 100-1000 xcexcm, preferably 100-500 xcexcm, and spherical beads as well beads of an irregular shape may be used, even if spherical beads are preferred as discussed below. The density of the beads is typically 1.10-1.50 g/ml, for instance around 1.15 g/ml (the values are given for hydrated beads).
The polymer is synthetic, for instance from mono- or polyvinyl monomers like acrylates, metacrylates or vinylbenzenes, or of natural origin, preferably a polysaccharide, for instance agarose, starch, cellulose or derivatives of these, optionally crosslinked for the desired rigidity and pore distribution.
The glass or silica particles to be incorporated are preferably in the range of from 1-100 xcexcm and may be spherical as well as of an irregular shape. The amount of silica particles incorporated into the polymer particles is in the range of from 5-50% of the weight of the wet final particle. In a preferred embodiment of the invention quartz particles are utilized.
One important characteristic of a carrier matrix to be used in down stream processing is that it is stable to the various solutions used for instance in reconditioning steps. Several applications require a strongly alkaline medium to be used for reconditioning and this has been found to be fatal to the prior art carrier matrices earlier tested. Especially in cases when the flow through the bed during the elution step is reversed to give a packed bed, even minor changes of the support matrix might cause serious problems resulting in lower yields, etc. In this elution technique spherical beads are preferred for improved elution capability. The reasons for this are well known to those skilled in the art.